High rates of relapse to drug use after prolonged drug-free periods characterize the behavior of people addicted to opioid and psychostimulant drugs. The behavioral and neurochemical events that contribute to these high relapse rates, however, are not well understood. Relapse can be induced in human subjects and laboratory animals by re-exposure to the drug previously used or re-exposure to environmental cues paired with drug self-administration. We are using different animal models of relapse to study brain systems and neurotransmitters involved in relapse induced by these stimuli in rats with a history of opioid (heroin, oxycodone, fentanyl) and psychostimulant (cocaine, methamphetamine) self-administration.